At this time, it appears that Novartis will submit Flucelvax trivalent bulk for in-support testing in September (exact date to be determined) prior to the approval date (which is currently projected for September 21, 2012). Given the amount of time needed for the in-support assays (approximately 2-3 weeks), there may not be sufficient time to complete this testing prior to approval. Furthermore, the timing of this submission would not afford any time for investigations, should problems arise during the testing. As such, CBER will consider the submission of the trivalent bulk samples as a major amendment. Although this will officially add three months to the approval date, we only plan to delay approval of Flucelvax long enough to complete testing and address any issues that arise. The new projected approval date will be determined after the major amendment is issued and will depend on the exact date the trivalent bulk samples are received by CBER. We will convey our new target date for approval shortly after the major amendment is issued.

Also, it is our understanding that the same trivalent samples that will be submitted in September will also represent lots for release. Since in-support testing, lot-release testing, and review of the strain change information can proceed concurrently, we recommend that you also submit the 2012-2013 strain-change information with the trivalent bulk samples. Although it may appear daunting, we believe that review of the strain change information and completion of the lot-release testing will not add further delay to approval beyond what is needed to complete the in-support testing. Therefore, we believe it is in Novartis' interest to submit the strain-change information concurrently with the trivalent bulk samples to support approval of the 2012-2013 United States formulation at the time of licensure of Flucelvax.

At your earliest convenience, please provide your target date for submission of the trivalent bulk samples and whether you agree with our recommendation to include the strain change information to support the 2012-2013 formulation with these samples.

Please let me know if you have any concerns or if any clarifications are needed.